etelcalcetide (Rx)

Brand and Other Names:Parsabiv
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

solution for injection (single-dose vials)

  • 2.5mg/0.5mL
  • 5mg/mL
  • 10mg/2mL

Hyperparathyroidism

Indicated for secondary hyperparathyroidism (SHPT) for patients with chronic kidney disease (CKD) on hemodialysis

Recommended dose

  • Ensure corrected serum calcium is at or above the lower limit of normal prior to initiation, a dose increase, or reinitiation of therapy after a dosing interruption
  • Starting dose: 5 mg IV bolus injection 3 times/week at the end of hemodialysis treatment
  • Also see Administration
  • Maintenance dose
    • Individualize and determine by titration based on parathyroid hormone (PTH) and corrected serum calcium response
    • The maintenance dose is the dose that maintains PTH levels within the recommended target range and corrected serum calcium within the normal range
    • Lowest maintenance dose: 2.5 mg IV 3 times/week
    • Highest maintenance dose: 15 mg IV 3 times/week

Monitoring

  • Monitor corrected serum calcium and PTH levels during dose initiation, dose adjustment, and dose maintenance
  • Corrected serum calcium levels
    • Obtain 1 week after dose initiation or dose adjustment
    • Obtain q4 weeks during maintenance
  • PTH levels
    • Obtain 4 weeks after dose initiation or dose adjustment
    • Obtain per clinical practice

Dose adjustment

  • Increase dose
    • Increase by 2.5- or 5-mg increments in patients with corrected serum calcium within the normal range and PTH levels above the recommended target no more frequently than q4 weeks
    • Maximum dose of 15 mg 3 times/week
  • Decrease or temporarily discontinue dosing
    • Patients with PTH levels below the target range
    • In individuals with a corrected serum calcium below the lower limit of normal, but ≥7.5 mg/dL without symptoms of hypocalcemia, consider decreasing or temporarily discontinuing the drug or use concomitant therapies to increase corrected serum calcium
    • If the dose is stopped, then reinitiate at a lower dose when PTH is within the target range and hypocalcemia has been corrected
  • Stop and treat hypocalcemia
    • Stop drug if the corrected serum calcium is <7.5 mg/dL or patients report symptoms of hypocalcemia
    • May reinitiate at a dose 5 mg lower than the last dose administered when corrected serum calcium is within normal limits, symptoms of hypocalcemia have resolved, and predisposing factors for hypocalcemia have been addressed
    • If the last administered dose was 2.5 mg or 5 mg, reinitiate at a dose of 2.5 mg

Switching from cinacalcet

  • Discontinue cinacalcet for at least 7 days before starting etelcalcetide
  • Initiate etelcalcetide at a starting dose of 5 mg IV bolus
  • Ensure corrected serum calcium is at or above the lower limit of normal prior to initiation

Dosing Considerations

Limitations of use

  • Has not been studied in adults with parathyroid carcinoma, primary hyperparathyroidism, or CKD who are not on hemodialysis
  • Not recommended for use in these populations

Safety and efficacy not established

Hyperparathyroidism (Orphan)

Orphan designation for treatment of pediatric hyperparathyroidism

Sponsor

  • Amgen, Inc; 1 Amgen Center Drive; Thousand Oaks, California 91320

No clinically significant differences in safety, efficacy, or etelcalcetide plasma concentrations were observed between patients ≥65 yr and younger patients

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Interactions

Interaction Checker

and etelcalcetide

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    Contraindicated

      Serious - Use Alternative

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            Adverse Effects

            >10%

            Decreased serum calcium, asymptomatic reductions in calcium <7.5 mg/dL or clinically significant asymptomatic reductions in corrected serum calcium between 7.5 and <8.3 mg/dL that required medical management (64%)

            Muscle spasms (12%)

            Diarrhea (11%)

            Nausea (11%)

            1-10%

            Vomiting (9%)

            Headache (8%)

            Hypocalcemia (7%)

            Paresthesia (6%)

            Hypersensitivity (4.4%)

            Hyperkalemia (4%)

            Hospitalization for heart failure (2%)

            Myalgia (2%)

            QTc prolongation secondary to hypocalcemia (1.2%)

            Hypophosphatemia (1%)

            <1%

            Hypocalcemia, symptomatic reductions in corrected serum calcium <8.3 mg/dL (0.2%)

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            Warnings

            Contraindications

            Known hypersensitivity to etelcalcetide or any of its excipients; hypersensitivity reactions, including pruritic rash, urticaria, and face edema, have occurred

            Cautions

            Cases of hypotension, congestive heart failure, and decreased myocardial performance reported in clinical trials; closely monitor for worsening signs and symptoms of heart failure

            Adynamic bone may develop if PTH levels are chronically suppressed; if PTH levels decrease below the recommended target range, the dose of vitamin D sterols and/or etelcalcetide should be reduced or discontinued; after discontinuation, resume therapy at a lower dose to maintain PTH levels in the target range

            Rare reports of upper GI bleeding occurred during clinical trials; the exact cause of the GI bleeds were unknown and there were too few cases (2 of 1253 patient-years of exposure) to determine if GI bleeding was related to etelcalcetide

            Hypocalcemia

            • Etelcalcetide lowers serum calcium and can lead to hypocalcemia, sometimes severe; low serum calcium can cause paresthesias, myalgias, muscle spasms, seizures, QT interval prolongation, and ventricular arrhythmia
            • Patients predisposed to QT interval prolongation, ventricular arrhythmias, and seizures are at increased risk of hypocalcemia and should be monitored closely; patients should be educated about the symptoms of hypocalcemia and should be advised to contact a healthcare provider if it occurs
            • Measure corrected serum calcium prior to initiation, within 1 week after initiation or dose adjustment, and then every 4 weeks (see Administration for dose adjustment)
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            Pregnancy

            Pregnancy

            There are no available data on the use in pregnant women

            Animal studies

            • In animal reproduction studies, effects were seen at doses associated with maternal toxicity that included hypocalcemia
            • In a prenatal and postnatal study in rats administered etelcalcetide during organogenesis through delivery and weaning, there was a slight increase in perinatal pup mortality, delay in parturition, and transient effects on pup growth at exposures 1.8 times the human exposure for the clinical dose of 15 mg 3 times/week

            Lactation

            Unknown if distributed in human breast milk

            Studies in rats showed distribution in milk at concentrations similar to plasma

            Because of the potential for etelcalcetide to cause adverse effects in breastfed infants, including hypocalcemia, use is not recommended while breastfeeding

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Calcimimetic agent that allosterically modulates the calcium-sensing receptor (CaSR)

            Etelcalcetide binds to the CaSR and enhances activation of the receptor by extracellular calcium

            Activation of the CaSR on parathyroid chief cells decreases PTH secretion

            Distribution

            Protein bound: Predominately bound to plasma albumin by reversible covalent binding

            Blood to plasma ratio: ~0.6

            Vd: 796 L

            Metabolism

            Biotransformed in blood by reversible disulfide exchange with endogenous thiols to predominantly form conjugates with serum albumin

            Not metabolized by CYP450 enzymes

            Elimination

            Half-life: 3-4 days

            Excretion

            • Normal renal function (volunteers in clinical trials): Cleared by renal excretion
            • Hemodialysis: Removed with a hemodialysis clearance value of 7.66 L/hr
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            Administration

            IV Preparation

            Do not mix or dilute prior to administration

            The solution is clear and colorless

            Inspect for particulate matter and discoloration prior to administration

            Do not use vial if particulate matter or discoloration is observed

            IV Administration

            Administer IV bolus injection into the venous line of the dialysis circuit at the end of the hemodialysis treatment during rinse back or IV after rinse back

            Administer only at the end of hemodialysis treatment

            Missed dose

            • If a regularly scheduled hemodialysis treatment is missed, DO NOT administer any missed doses
            • Resume dose at the end of the next hemodialysis treatment at the prescribed dose
            • If doses are missed for >2 weeks, reinitiate at the recommended starting dose of 5 mg (or 2.5 mg if that was the patient’s last dose)

            Storage

            Store in the original carton in refrigerator at 2-8°C (36-46°F) to protect from light

            Once removed from the refrigerator

            • Do not expose to temperatures >25°C (77°F)
            • Use within 7 days if stored in the original carton
            • Use within 4 hr and do not expose to direct sunlight if removed from the original carton
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            Formulary

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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